Cognition Therapeutics Inc. announced the discovery of a new drug target in the brain that plays a role in the development of Alzheimer’s disease, and their investigation of new drug candidates to reverse the memory loss associated with Alzheimer’s.
The two studies were entitled “Alzheimer’s therapeutics targeting Amyloid beta 1-42 oligomers I: Abeta oligomers binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits” and “Alzheimer’s therapeutics targeting Amyloid beta 1-42 oligomers II: sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity.“ Both were published in the PlosOne journal.
In the first study, the authors report the finding of a new receptor associated with Alzheimer’s disease — sigma-2/PGRMC1 (progesterone receptor membrane component 1) — by mediating the attachment of Amyloid beta oligomers to neurons, disrupting their normal function and leading to memory loss. They developed further functional studies and generated novel therapeutic antagonists against the receptor that were able to block the toxicity effects of Amyloid beta both in vitro and in vivo — notably, synapse loss in vitro and cognitive deficits in AD mouse models.
In the second study, the authors report their screening studies in mature, in vitro cultures of rat brain cells to identify specific compounds that inhibit the accumulation of Amyloid beta oligomers. They identified compounds that target and bind Sigma-2/PGRMC1 receptor protein with high affinity and specificity, therefore saturating its binding capacity and preventing binding of damaging amyloid beta oligomers.
Dr. Susan Catalano CSO Cognition Therapeutics commented, “Our approach is fundamentally different from that of other therapeutics in development such as BACE inhibitors and monoclonal antibodies targeting Abeta protein, which focus on reducing the levels of Abeta in the brain. We discovered that Abeta oligomers bind very specifically and saturably to the sigma-2/PGRMC1 receptor or proteins that are tightly controlled by it. When our compounds bind to sigma-2/PGRMC1 receptors, they alter it so that the oligomers can no longer bind or are actually kicked off if they are already bound. One of these molecules are our investigational new drug candidate whom we hope will be in the clinic next year. This molecule represents the first opportunity to test directly this target together with the hypothesis that soluble toxic Abeta oligomers interact with this receptor on brain’s nerve cells to cause memory loss in Alzheimer’s disease.”
Hank Safferstein, Cognition Therapeutics’ CEO added, “Taken together the exciting implication of these findings is that the investigational agents we have discovered and are currently developing give the promise of not only reversing the memory and learning defects in patients diagnosed with Alzheimer’s disease but also of slowing or even halting disease progression. This would be a quantum leap in mechanism of action from the currently used anti-Alzheimer’s agents who are at best only mildly symptom reducing. Disease modification is the Holy Grail of Alzheimer’s research, and we believe our drugs give new hope of a meaningful and lasting benefit to patients diagnosed with Alzheimer’s disease and their caregivers.”